Dietary fiber guar gum-induced shift in gut microbiota metabolism and intestinal immune activity enhances susceptibility to colonic inflammation

Abstract

With an increasing interest in dietary fibers (DFs) to promote intestinal health and the growth of beneficial gut bacteria, there is a continued rise in the incorporation of refined DFs in processed foods. It is still unclear how refined fibers, such as guar gum, affect the gut microbiota activity and pathogenesis of inflammatory bowel disease (IBD). Our study elucidated the effect and underlying mechanisms of guar gum, a fermentable DF (FDF) commonly present in a wide range of processed foods, on colitis development. We report that guar gum containing diet (GuD) increased the susceptibility to colonic inflammation. Specifically, GuD-fed group exhibited severe colitis upon dextran sulfate sodium (DSS) administration, as evidenced by reduced body weight, diarrhea, rectal bleeding, and shortening of colon length compared to cellulose-fed control mice. Elevated levels of pro-inflammatory markers in both serum [serum amyloid A (SAA), lipocalin 2 (Lcn2)] and colon (Lcn2) and extensive disruption of colonic architecture further affirmed that GuD-fed group exhibited more severe colitis than control group upon DSS intervention. Amelioration of colitis in GuD-fed group pre-treated with antibiotics suggest a vital role of intestinal microbiota in GuD-mediated exacerbation of intestinal inflammation. Gut microbiota composition and metabolite analysis in fecal and cecal contents, respectively, revealed that guar gum primarily enriches Actinobacteriota, specifically Bifidobacterium. Guar gum also altered multiple genera belonging to phyla Bacteroidota and Firmicutes. Such shift in gut microbiota composition favored luminal accumulation of intermediary metabolites succinate and lactate in the GuD-fed mice. Colonic IL-18 and tight junction markers were also decreased in the GuD-fed group. Importantly, GuD-fed mice pre-treated with recombinant IL-18 displayed attenuated colitis. Collectively, unfavorable changes in gut microbiota activity leading to luminal accumulation of lactate and succinate, reduced colonic IL-18, and compromised gut barrier function following guar gum feeding contributed to increased colitis susceptibility.

Keywords: Added fiber; Bifidobacterium; dysbiosis; inflammatory bowel disease; interleukin-18 (IL-18); lactate; succinate.

Figure 1.

Guar gum exacerbated DSS-induced acute colitis.

Figure 2.

Antibiotic-mediated depletion of gut microbiota rescued GuD-fed mice from DSS-induced colitis.

Figure 3.

Guar gum fed mice displayed shift in gut microbiota enriching Actinobacteriota.

Figure 4.

Guar gum-induced alterations in gut microbiota metabolism was associated with luminal accumulation of intermediate metabolites, including lactate and succinate.

Figure 5.

Guar gum suppressed the colonic mRNA expression of mucins and mucosal barrier proteins.

Figure 6.

Guar gum-fed mice displayed reduced expression of colonic IL-18.

Figure 7.

Exogenous IL-18 administration reduced colitis severity in GuD-fed mice.